Table 1. Metastasis suppressors and proposed mechanisms.
| Metastasis suppressor | Proposed Mechanism(s) of Action | Step(s) in Metastasis implicated |
|---|---|---|
| BRMS1 | Transcriptional regulation via interaction with SIN3:HDAC complexes; down-regulates PtdIns(4,5)P2 | Invasion (Intravasation/Extravasation) Motility Adhesion Colonization |
| Caspase 8 | Induction of apoptosis if cells bind to un-liganded integrins | Transport Survival in circulation Adhesion |
| E-cadherin | Cell: cell interactions | Local invasion Intravasation |
| N-cadherin | Cell: cell interactions | Local invasion Intravasation |
| Cadherin-11 | Cell: cell, cell: matrix interactions | Local invasion Intravasation Motility |
| Caveolin-1 | Altering caveolae function | Invasion (Intravasation/Extravasation) Possibly colonization |
| CD44 | Hyaluronic acid receptor; osteopontin receptor stem cell marker (selected) | Adhesion Invasion Possibly colonization |
| DCC | Regulates cytoskeletal organization; regulates MAPK signaling | Motility Invasion (Intravasation/Extravasation) Survival in circulation |
| DLC1 | Rho-GTPase activating protein; regulates cytoskeletal structure | Motility Invasion (Intravasation/Extravasation) Survival in circulation |
| DRG1 | Unknown | Angiogenesis Possibly colonization |
| Gelsolin | Regulates cytoskeletal structure; reduces motility | Motility Adhesion Invasion (Intravasation/Extravasation) |
| HUNK | Protein kinase | Motility Invasion (Intravasation/Extravasation) |
| KAI1 | Interacts with endothelial DARC to induce apoptosis | Intravasation Survival in circulation |
| KISS1 (kisspeptins) | Maintains dormancy at secondary sites | Colonization |
| KISS1R | G-protein coupled receptor | Colonization |
| KLF17 | Transcription | Invasion (Intravasation/Extravasation) Local Invasion |
| LSD1 | Chromatin remodeling | Motility Invasion (Intravasation/Extravasation) Possibly colonization |
| MKK4 | Stress-Activated MAPK signaling | Colonization |
| MKK7 | Stress Activated MAPK signaling | Colonization |
| p38 | Stress Activated MAPK signaling | Colonization |
| Nm23 | Phosphorylates KSR to prevent downstream activation of MAPK pathways | Motility Invasion (Intravasation/Extravasation) Colonization |
| OGR1 | GPCR signaling | Invasion (Intravasation/Extravasation) Migration Possibly colonization |
| RhoGDI2 | Regulates Rho; negatively alters endothelin 1 and neuromedin U expression | Adhesion Invasion (Intravasation/Extravasation) Survival in circulation Possibly colonization |
| RKIP | Competitive inhibitor of RAF1-MEK interactions | Motility Invasion (Intravasation/Extravasation) Adhesion |
| RRM1 | Increases PTEN expression; decreases FAK phosphorylation | MotilityInvasion (Intravasation/Extravasation) Adhesion |
| SSeCKS | Scaffold protein for PKA and PKC; inhibits osteopontin, VEGF expression; up regulates vasostatin | Angiogenesis Adhesion Migration Invasion (Intravasation/Extravasation) |
| TIMPs | Inhibit metalloproteinases; signaling | Local invasion Invasion (Intravasation/Extravasation) Adhesion Colonization Angiogenesis |
Adapted from Hurst and Welch [1]